A randomized, double-blind, duloxetine-referenced study comparing efficacy and tolerability of 2 fixed doses of vortioxetine in the acute treatment of adults with MDD.

RATIONALE

Vortioxetine has reduced depressive symptoms in adults with major depressive disorder (MDD) in multiple clinical trials.

OBJECTIVES

The aim of this study is to evaluate the efficacy, safety, and tolerability of vortioxetine 15 and 20 mg vs placebo in adults with MDD.

METHODS

Patients were randomized 1:1:1:1 to vortioxetine 15 mg, vortioxetine 20 mg, duloxetine 60 mg (active reference), or placebo. The primary efficacy endpoint was mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 8 (MMRM). Safety/tolerability assessments included physical examinations, vital signs, laboratory evaluations, electrocardiograms, adverse events (AEs), Columbia-Suicide Severity Rating Scale, Arizona Sexual Experiences Scale, and Discontinuation-Emergent Signs and Symptoms checklist.

RESULTS

Six hundred and fourteen patients were randomized. Mean changes in MADRS scores were -12.83 (±0.834), -14.30 (±0.890), -15.57 (±0.880), and -16.90 (±0.884) for placebo, vortioxetine 15 mg (P = .224), vortioxetine 20 mg (P = .023), and duloxetine 60 mg (P < .001) (P vs placebo), respectively. AEs reported by ≥5 % of vortioxetine patients included nausea, headache, diarrhea, dizziness, dry mouth, constipation, vomiting, insomnia, fatigue, and upper respiratory infection. Treatment-emergent sexual dysfunction, suicidal ideation or behavior, and discontinuation symptoms were not significantly different between vortioxetine and placebo.

CONCLUSIONS

Vortioxetine 20 mg significantly reduced MADRS total scores after 8 weeks of treatment. Both vortioxetine doses were well tolerated.

CLINICAL TRIAL REGISTRATION

ClinicalTrials.gov identifier NCT01153009; www.clinicaltrials.gov/ .